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Arterial Blood Gas Monitoring
RESPIRATORY PROCEDURES AND MONITORING
0749-0704/95 $0.00 + .20
ARTERIAL BLOOD GAS MONITORING Hugh C. Gilbert, MD, and Jeffery S. Vender, MD, FCCM
Blood gas determinations (ABGs) play an important role in diagnosing potentially life-threatening derangements in acid-base balance, oxygenation, and ventilation. Managing critically ill patients requires frequent assessment of ABGs. This article reviews the technologic evolution of modern blood gas analysis and the clinical application of monitoring hydrogen ion content (pH), blood oxygen tension (Po2 ), and carbon dioxide tension (Pco 2). For many years, ABGs have been performed in specialized laboratories. Prior to the development of the modern acid-base laboratory (defined as integrated equipment that measures "blood gases"), monitoring cardiopulmonary homeostasis was difficult. Until the development of electrochemical sensors, clinicians were unable to assess ABGs routinely. Manometric and volumetric determinations of the "gas" content of blood were available in specialized areas of the hospital but the equipment was too cumbersome and impractical to be considered for monitoring critically ill patients. Table 1 illustrates the chronology of ABGs to the development of electrochemical sensors. During the past 20 years, the most significant advance in in vitro blood gas analysis has been due to the miniaturization and automation of microprocessorcontrolled instruments that simplify the process of blood gas measurements. The components of a modern blood gas machine include: 1. a gas mixer that produces calibrating gases containing known
partial pressures of 0 2 and C0 2; 2. a measurement section that contains valves, tubing, pumps, and From the Department of Anesthesiology (HCG, JSV), Northwestern University Medical School, Chicago; Medical-Surgical Intensive Care Unit GSV); and Division of Anesthesiology (HCG, JSV), Evanston Hospital, Evanston, Illinois
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Table 1. THE CHRONOLOGY OF THE BLOOD GAS LABORATORY Date
< 1950 1957 1957 1958 1970
Development Gas analysis Sanz electrode Stow electrode Severinghaus electrode IL co-oximeter
Methodology
Measurement
Volumetric Mano metric Electrochemical Electrochemical Electrochemical Spectrophotometric
Oxygen content Carbon dioxide content pH Pco2 Pco2 Hbo2, Hbco
Pco2 = carbon dioxide tension ; Hbo2 = hemoglobin oxygen content; Hbco = hemoglobin carbon monoxide.
heaters that transport the sample under controlled conditions to an electrode bank where the measurements are made; 3. a rinsing section containing the maintenance solutions that refresh the electrode bank following each measurement; and 4. an electronics section that monitors the other components, controls the movement of gases and liquids, initiates calibrations, performs diagnostic tests, and prints a report of the analysis and status of all instrument functions. Instruments of this description have been available for clinical practice for 20 years. Today's automated blood gas analyzers use specialized electrochemical sensors for measuring pH, Pco 2, and Po2 • The pH and Pco 2 electrodes quantify the difference in pH between two solutions using an electrolytic circuit. At 37°C, a properly functioning pH electrode will register a 61.5 m V change for each pH unit difference between a known buffer solution and the unknown blood sample. The voltage change can be calculated by a modification of the Nernst equation. The Pco2 electrode uses the same design concept as that for pH. A typical Pco2 electrode contains a pH electrode that is separated from the blood sample by a C0 2 permeable membrane. A buffer solution of sodium bicarbonate (NaHC03 ) and sodium chloride (NaCl) resides on the sample side of the pH electrode. As the C0 2 gas crosses the membrane, the pH of the buffer changes in proportion to the partial pressure of C02 crossing the membrane. Most blood gas analyzers contain a Clark electrode for measuring the partial pressure of oxygen. The Po2 electrode is based on the oxidation-reduction reaction of dissolved oxygen and water. The reaction requires a constant supply of electrons, which are provided by a polarizing voltage applied to a silver wire. For this reason, the Clark electrode also is called a polarographic electrode. An oxygen-permeable membrane isolates the electrode system, reducing the effect of plasma proteins on the reaction. At a platinum cathode, oxygen combines with four electrons. Under these circumstances, the electrode current depends on the reduction of oxygen at the platinum electrode: I = S x Po2 + Io, where S is the sensitivity and Io is the current when Po2 = 0. These three electrodes represent the basic components used to measure ABGs. Modern blood gas analyzers initiate calibration sequences
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automatically at preprogrammed intervals. During calibration, the estimated value for the analyte of interest is compared with a theoretical value based on the measured barometric pressure and the calculated value of the partial pressure of the calibrating gas mixture. The performance of a blood gas analyzer must be evaluated periodically to ensure that the estimates are accurate.7 ERRORS OF ANALYSIS AND PERFQRMANCE CRITERIA
Laboratory instruments must comply with three performance criteria: Accuracy defines the nearness of a measurement to the actual value of the variable being measured, bias represents a consistent difference of the variable, and precision defines the closeness of the measurement. 25 The electrochemical sensors employed in blood gas analyzers are expected to have a high degree of precision. Wickers et al compared the precision of three common systems;33 Table 2 lists the laboratory precision observed in this study for electrochemical sensors measuring known analytes in a short time frame. Electrochemical sensors drift over time. Modern instruments perform single point calibration to stabilize electrode performance, reducing the importance of drift as a source of inaccuracy. Blood gas laboratories are required to enroll in proficiency testing.7 One such program is operated by the American Thoracic Society (ATS). ATS testing uses a fluorocarbon emulsion that serves as an artificial blood control. Samples are sent to participating laboratories and the results from the participating laboratories are compared. An instrument report is generated for each laboratory and a rating is assigned based on the statistical analysis of the ranges of values submitted by the participants. Proficiency testing documents the bias of blood gas instruments and their operators. Testing programs ensure clinicians that ABG measurements have an acceptable accuracy and precision.7 Inter- and intrainstrument variability is expected to occur within prescribed boundaries. Table 3 lists the proficiency limits accepted by the College of American Pathologists and the Health Care Financing Administration. 6• 13 Stand-alone instruments have an advantage over in vivo or in continuity instruments because it is always possible to assess clinical performance and sensor drift during the period of clinical usage by performing Table 2. PRECISION OF ELECTROCHEMICAL SENSORS Electrode
Measurement
Sanz Severinghaus
pH Pco2
± 0.01 pH unit ± 2%
Clark
Po2
± 1 mm Hg at 40 mm Hg ± 3% ± 2.5 mm Hg at 80 mm Hg
Precision
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Table 3. PROFICIENCY TESTING LIMITS FOR BLOOD GAS LABORATORIES* Parameter
CAP Limits
HCFA Limits
pH PC02 Po2
± 0.03 ± 3 mmHg ± 7.5%
± 0.04 ± 5 mmHg ± 3 SD
CAP = College of American Pathologists; HCFA = Health Care Financing Administration ; Pco, = carbon dioxide tension ; Po, = blood oxygen tension. pH is reported in pH units. SD refers to the standard deviation of the proficlency testing group. ·A blood gas laboratory refers to the instrument and its operator. From Shapiro BA: Evaluation of blood gas monitors: Performance criteria, clinical impact, and cost/ benefit. Grit Care Med 22:546-548, 1994; with permission.
periodic calibrations. In vivo sensors are designed to be calibrated prior to their insertion. Other factors can influence the accuracy of an ABG measurement or its clinical interpretation. TEMPERATURE CORRECTION
Temperature correction represents the most important physical factor that may influence clinical interpretation of ABGs. The effects of temperature and pressure are operational for all methodologies currently employed for measuring ABGs. Blood gas analysis is carried out at 37°C. Temperature influences gas solubility, ion dissociation, and the offloading of oxygen from hemoglobin. As a general guideline, Po2 and Pco2 decrease (ideal gas law) and pH increases when temperature falls below 37°C. Table 4 lists the changes of the ABG analytes as a function of temperature. Temperature correction may be of clinical importance in patients whose temperatures are outside the range of 35° to 39°C. Blood gas analyzers report the results of analysis corrected to 37°C. Most analyzers can report their results at any patient temperature. Table 4. THE EFFECT OF TEMPERATURE ON pH , CARBON DIOXIDE TENSION , AND BLOOD OXYGEN TENSION MEASUREMENTS Temperature
oc
OF
pH
Pco.
Po 2
20 30 35 36 37 38 40
68 86 95 97 98 100 104
7.65 7.50 7.43 7.41 7.40 7.39 7.36
19 30 37 38 40 42 45
27 51 70 75 80 85 97
Pco, = carbon dioxide tension; Po, = blood oxygen tension . From Shapiro, Peruzzi , Kozelowski-Templin: Clinical Application of Blood Gases, ed 5. St. Louis, Mosby-Year Book, 1994, p 128; with permission .
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The clinical importance of temperature correction versus reporting the results at the patient's measured temperature is still hotly debated. Clinicians who use uncorrected ABGs subscribe to the concept of alpha stat interpretation. Alpha refers to the histidine imidazole locus on hemoglobin, which plays a central role in the ability of hemoglobin to buffer pH changes during oxygen transport. In vitro studies suggest that, following cooling, the pH of amphibian blood behaves in a manner similar to that of aqueous solutions containing carbonic acid, bicarbonate (HC0 3), and imidazole. 22 Poikilothermi~ species do not correct their pH during cooling. On the other hand, hibernating animals maintain their blood pH during cooling by increasing their C02 content. The strategy whereby C0 2 is added to maintain pH during deep hypothermia is based on the premise that hypothermic humans should behave in the same way as hibernating species. This management plan has been termed pH stat. Animal studies indicate that pH stat management often results in excessive alkalemia when hypothermic animals are administered NaHC0 3 to correct the "normalized pH" during rewarming.3 pH Stat management has been associated with depressed myocardial contractility during rewarming. On the other hand, pH stat proponents believe that cerebral perfusion is preserved best by normalizing pH during hypothermia. Altering temperature affects the solubility of oxygen as well as hemoglobin's affinity for oxygen. Changing blood temperature will influence the Po 2 but does not change the measured oxygen content. In response to a decreasing temperature, hemoglobin increases its affinity for oxygen (a leftward shift of the oxyhemoglobin dissociation curve), resulting in a decrease in oxygen tension. Conversely, increasing temperature decreases the affinity of hemoglobin for oxygen, resulting in enhanced off-loading and an increase in Po2 • The importance of this temperature effect is demonstrated in Table 4, in which an arterial blood sample at 30°C has a measured Po2 of 51 mm Hg, equivalent to measuring 80 mm Hg at 37°C. Oxygenation is best evaluated at the standard 37°C values because the actual temperature is rarely determined at the time of sampling. The effect of fluctuating temperature on metabolism, vascular function, and respiration in critically ill patients is complex. Blood gas measurements use standard conditions (known as BTPS), in which 37°C represents the standard normal body temperature and pressure represents the atmospheric pressure to which the body is exposed fully saturated with water.1
ARTERIAL BLOOD GAS SAMPLING
Until recently, ABGs required intermittent blood gas sampling, using either an indwelling arterial cannula or direct arterial puncture. In critically ill patients, it is common to require frequent sampling to monitor ABG derangements and their response to therapy. Blood gas samples are susceptible to sampling errors.2 Until the introduction of
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point-of-care and in vivo methodologies, ABC analysis required obtaining a blood sample and transporting it to the location where analysis occurred. Historically, issues such as the composition of syringe, the chemistry of the anticoagulant, and the conditions used for transport have been raised and evaluated. Although plastic syringes may absorb oxygen at partial pressures above 400 mm Hg, they are in common use. Today, heparin is the anticoagulant of choice. Most heparins have a pH of approximately 7. Clinicians and their support staff have been trained to reduce the potential of introducing sampling errors when obtaining ABCs. Blood samples must be obtained under strict anaerobic conditions and be placed on ice and held at 0°C until analysis. Air bubbles interfere with the accuracy of gas analysis. Contamination with room air raises the estimate of the Po2 and lowers the Pco2 when sampled from normal subjects breathing room air. The effect of room air contamination (Po2 = 150; Pco2 = 0) depends on the physiologic conditions present at the time of sampling and oxygen delivery. Icing the sample eliminates the influence of metabolically active white cells present in the sample. Spontaneous changes in oxygen consumption, cardiac output, and the systemic distribution of blood flow have been implicated as factors that may influence the variability of ABC values observed in clinically stable patients who have undergone frequent blood gas sampling.
INSTRUMENT VARIABILITY
The issue of the analysis and interpretation of blood gas instrument similarities and differences is complex. Of the analytes in question, the Po2 value often is disparate when comparing a sample analyzed on different instruments. Hansen and colleagues 12 compared the biases of six models of blood gas instruments in common usage. Their studies demonstrate that instrument variation is quite common and quality control analytes tend to overestimate instrument bias compared with tonometered blood. 12
THE VALUE OF BLOOD GASES
Accurate knowledge of pH, Pco2 , Po2 , and total hemoglobin in both arterial and pulmonary blood has been very helpful in clinical decision making. Indices such as oxygen content (Cao2), HC03, base excess, and oxyhemoglobin saturation can be derived mathematically from ABC analysis. Parameters such as arterio-venous oxygen content differences (C(a-v)o2 ) and intrapulmonary shunt can be calculated from arterial and venous gas analysis. These factors play an important role in evaluating overall cardiopulmonary function and tissue oxygenation. When ABC analysis is combined with multiwavelength oximetry, active hemoglobin concentration, total oxygen concentration, actual half-satura-
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tion tension, and 2,3-diphosphoglycerate concentration can be estimated mathematically. 30 This suggests that routine ABGs and multiwavelength oximetry contain significant information concerning the oxygen status of patients. In critical care units, monitoring arterial oxygenation is a clinical imperative. The maintenance of cellular oxygenation depends on an effective cardiac output (CO), perfusion, and arterial Cao2 • Cao2 is calculated using the following formula: Cao2 = (Pao2
X
0.003)
+ Hb
X
Sao2
X
1.34) vol %,
where Hb is hemoglobin and Sao 2 is arterial oxygen percent saturation. The capability of critically ill patients to maintain tissue oxygenation is quantified by calculating oxygen delivery (00 2 ): 002
=
Cao2 x CO
The information gained by monitoring cardiovascular and metabolic influences on tissue oxygen balance is enhanced by calculating the oxygen content of both arterial and mixed-venous blood. Healthy patients have an oxygen content difference, C(a-v)o2 , of 5 vol %. Critically ill patients frequently have derangements in cardiac performance associated with increasing tissue oxygen demands, which may result in a decrease in C(a-v)o2 • Dual oximetry (using methods to monitor Sao2 and Svo2 continuously) has been proposed to be helpful in monitoring critically ill patients.4 Inadequate Do 2 or inadequate tissue perfusion results in tissue hypoxia and the development of lactic acidemia. Blood pH is essentially determined by the HC0 3 / carbonic acid relationship, the interplay of alterations in Pco 2 (ventilatory changes), and a metabolic component defined by the variance from the normal buffer base related to alterations in normal homeostasis. Clinically important acidemia is potentially life-threatening because of disturbances in essential enzyme systems and electrolyte balance. Autonomic receptors also are affected and the responses of exogenous drugs on receptor activation become unreliable. The interplay of the factors just mentioned defines the importance of ABG analysis in the clinical assessment of critically ill patients. 29 Po 2 Analysis is necessary to determine the presence or extent of hypoxernia, helps define the off-loading and uptake of oxygen by hemoglobin, and is essential in calculating oxygen delivery to the tissues. Po2 Analysis is essential for differentiation of pulmonary and cardiovascular factors that contribute to hypoxemia. Calculation of alveolar-to-arterial oxygen tension (P(A - a)o2 ) has important historical considerations as an index for quantifying disturbances in pulmonary oxygen transfer. Calculation of the shunt fraction has displaced the A - a gradient because it is more reliable in acutely ill patients. Shunt fraction requires pulmonary artery catheterization and measuring arterial and venous oxygen tensions. Blood pH measurement defines the presence or absence of acidernia or alkalernia. Ventilatory homeostasis is determined by assessment of
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the pH and Pco2. Inadequate alveolar ventilation is defined by the failure of ventilation to satisfactorily meet the demands of C02 excretion. C02 homeostasis in the critically ill is complicated by ongoing alterations in C02 production as well as peripheral stores. Compensated states frequently are encountered, in which pH is apparently normal, but significant increases are seen in peripheral and central C02 stores. Critically ill patients frequently demonstrate increases in dead space ventilation (V 0 ). V0 often is found in patients with cardiac failure, pulmonary embolus, pulmonary hypertension, and acute lung injury. Physiologic dead space is expresseo as a ratio of dead space-to-tidal volume (VT) and is calculated from the Bohr equation, where: Vo/ VT = (PaC02 - PEC02) I PaC02 PEC02 is expired C02. C02 homeostasis in the critically ill may be complex because C02 production and C02 peripheral stores may be abnormal. C02 production is increased approximately 10% per degree centrigrade rise in temperature. Shivering, rigor, or frank seizures can affect C02 production as well as oxygen consumption. Patients with head injuries or other central nervous system insults may demonstrate acute alveolar hyperventilation, resulting in depletion of central and peripheral C02 stores. Chronic hypercarbia also is multifactorial. Factors such as chronic obstructive pulmonary diseases, heredity, central chemoreceptor unresponsiveness to C02, and diminished myocardial reserves have been demonstrated to affect Pco2 and acid- base balance. ABC analysis therefore has a central place in the integration of pulmonary and cardiovascular homeostasis in critical care medicine. Monitoring represents the process by which clinicians recognize and evaluate dynamic physiologic processes in a timely manner. The term is derived from monere, which means to warn, remind, or admonish. The goal of ABC monitoring is to enhance clinical judgments regarding pulmonary and cardiovascular homeostasis by identifying changes in pH, Pco2, Po2, and all their derived parameters, almost continuously. Blood gas analyzers require the removal of blood and cannot be thought of as patient monitors unless they are dedicated to a specific patient and analysis is performed minute by minute. Blood gas analyzers can be miniaturized so they can become point-of-care instruments. Frequent use of point-of-care instruments can provide updates of ABCs and reduce the time between analysis and therapy. In this article, the term ABG monitor infers that the instrumentation is dedicated to a particular patient; updates the variables of interest at clinically appropriate intervals, automatically; can graphically trend pH, Pco2, and Po2; and operates without permanently removing blood from the patient. ABC monitoring presumes all the inherent risks and benefits of arterial cannulation. Table 5 summarizes some of the design constraints inherent in developing clinically useful ABC monitors. An ideal ABC monitor would provide continuous measurements, allowing for setting of alarm limits that alert the intensive care unit management team to initiate proactive
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Table 5. DESIGN CONSTRAINTS FOR BLOOD GAS MONITORS Have accuracy and performance comparable to ABG analyzers Be operable with a 20-gauge arterial catheter Permit simultaneous and continuous arterial pressure monitoring Must be biocompatible with blood Minimize the potential for thrombosis Be capable of seamless operation in an intensive care unit environment
Have a useful period of operation (72hour minimum) Perform accurately at low arterial blood flow Have thermal stability Be cost-effective
therapeutic interventions faster than is commonly achievable using blood gas analyzers. Several methodologies for estimating arterial blood gases have been adapted to develop instruments that can determine blood gases in vivo. In 1980, Richman and colleagues24 reported on using a specialized arterial probe and a portable gas chromatograph to continuously monitor ABG analytes. The probe was 15.2-cm long and had an external diameter of 0.07 cm. The technology did not meet the design characteristics necessary for in vivo monitoring because the system did not incorporate pH, the probe was cumbersome and large, vascular occlusion occurred, and the estimates of arterial oxygen pressure (Pao2 ) were affected by nitrous oxide. Gas transfer techniques (chromatography or mass spectrometry) do not appear to meet the criteria for clinical practice. Currently, there is no significant ongoing attempt to develop continuous, intra-arterial blood gas monitors (CIABGMs) based on gas transfer technology. On the other hand, systems using fiberoptics have undergone extensive investigation. 10 Glass or plastic fibers are ideal cables for indwelling sensing systems. They are isolated electrically and transport light by the phenomenon of total internal reflection. Measurements depend on the interaction of light with an indicator complex. To measure in vivo ABGs using fiberoptics, fiberoptic sensors for pH, Pco2 , Po2 , and a means to measure temperature (usually a thermocouple) must be designed to fit within a 20-gauge arterial cannula. A fiberoptic sensor system should allow continuous blood pressure monitoring, permit the intermittent sampling of blood for other analytes, and perform accurately without causing any increase in the risk of thrombosis within the artery or cannula for a period of 72 hours of usage in order to be a feasible replacement of current methods of surveying ABGs. 27 The following is a brief review of the scientific basis for fiberoptic measurement of ABGs. Light can be transmitted through optical fibers and is either absorbed or reflected. If the light is transmitted to an optically sensitive dye, the indicator may react with the light. Two reactions are possible. The indicator may change the character of the light by absorption, or the indicator can change the character of the light by becoming stimulated to fluoresce . Most fiberoptic systems designed for measuring ABGs use oxygen- and pH-sensitive dyes in their sensors.
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In a fluorescence-based sensor (Po2 ), an excitation signal (fluorescence) returns through the fiber. For oxygen, the intensity of this signal is inversely proportional to the concentration of oxygen in the arterial stream. Oxygen "quenches" the intensity of the fluorescence of the Po2 sensor dye. The intensity of the fluorescence therefore is least when oxygen tension is highest. Systems using oxygen quenching experience signal-noise disturbances at high oxygen tension. Absorbance-based sensors (pH, Pco2 ) transmit incident light to a dye cell.35 The dye absorbs the incident light based on the concentration of the analyte in question and the instrument measures the intensity of the light ·transmitted back through an optical transmission fiber. In a manner similar to that of the Severinghaus electrode, Pco 2 sensors incorporate an intermediate buffer layer between the blood interface and an optical pH-sensitive dye. Figure lA and B graphically depict the
Incident light
Dye cell
Transmitted light
--._/-~
- -··- A
Return (re-emitted) light signal
Dye
Excitation light signal
Figure 1. A, Diagram of an absorbance-based optical sensor. Absorbance-based optical sensors send light through the fiber to a dye cell. At the dye cell , the incident light is absorbed by the dye matrix. This degree of absorbance is a function of the concentration of the analyte of interest. The intensity of the returning unabsorbed light is proportional to the concentration of the analyte of interest. (Courtesy of the Puritan-Bennett Corporation, Carlsbad, CA) 8 , Diagram of a fluorescence-based optical sensor. Fluorescence-based optical sensors transmit an excitation light energy down the fiber. The dye at the tip reacts to the excitation light by fluorescing . The concentration of the analyte of interest influences the intensity of the fluorescence . The fluorescent signal then returns in the same fiber to the monitor, which measures the returning fluorescent signal. (Courtesy of the PuritanBennett Corporation, Carlsbad, CA)
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methodologies used in optical blood gas instruments. Absorbance-based sensors are similar to spectrophotometric laboratory devices in common use. Intravascular monitoring has posed major challenges to instrument designers. Electrochemical sensors have been designed to accommodate the size constraint. Microelectrodes (MEs) require electrical connections. Issues such as drift, intravascular fouling of surfaces, wire breakage, current leakage, and corrosion are significant constraints for the development of a clinically useful electroche~ical, in vivo, ABG monitor. Because the conditions of the measurement environment cannot be controlled intravascularly, microelecrodes must remain stable following calibration and insertion. Investigational devices have been designed and preliminary data on their performance characteristics have been reported. Eberhard et al 9 reported on the development of an ME for intravascular monitoring of oxygen. In 1988, Pfeifer, Pearson, and Clayton20 published their experience with an intra-arterial oxygen electrode in nine patients undergoing cardiac surgery. This report demonstrated that MEs for monitoring Po2 can perform well for short periods of time (> 26 hours). MEs having diameters approaching 2 µ,m have been designed for measuring cellular pH. Likewise, Pco2 MEs are feasible technically. Nearman and colleagues17 studied a Po2-Pco2 indwelling ME that uses miniature noble metal electrodes housed in chambers isolated by a biocompatible membrane. The system appears to have performance characteristics similar to fiberoptic sensors but has the advantage of lower production costs. A current version monitors pH, Pco2, and Po2. Fiberoptic chemical sensors (FOCS) are ideally suited to the intravascular environment. 19• 21 Reagents can be embedded in a matrix or encapsulated and bonded to the sensor probe. Optical fiber performance can be improved by coatings that enhance performance, strength, and blood compatibility. These membranes confine excitation and signal emissions, reducing optical noise resulting from naturally fluorescent molecules present at the probe-blood interface. FOCS probes may have a size advantage over MEs, making it possible to bundle several together for placement within arterial catheters. Electrical isolation also is a very desirable characteristic. FOCS-based systems have been designed for continuous intravascular applications. The first application was the design of ex vivo blood probes for monitoring ABGs in extracorporeal tubing. 20 These instruments were the first to demonstrate the benefits of continuous ABG monitoring. Although first-generation models did not perform as well as blood gas instruments, over time, these devices have become part of the standard extracorporeal set-up in many centers. The same FOCS system was modified to permit continuous, intravascular monitoring of ABGs. Bench studies of the intravascular system (CDI-1000, CDI-3M Healthcare, Irving, CA) using heparinized bovine blood demonstrated good correlation with standard measurements. Animal studies also were encouraging. The probe's performance warranted
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further study. The in vivo FOCS monitored physiologic changes in blood gas values as they occurred and was not adversely influenced by commonly infused drugs or anesthetic agents.15• 16 Preliminary evaluations in human subjects demonstrated that in vivo FOCS could identify changes in ABGs as they occur and significantly reduce the lag time for interpretation, to approximately 3 minutes. Comparison data suggest that Pco2 and pH estimates are virtually equivalent to standard laboratory estimates. The investigators of early FOCS systems were concerned with the potential for imprecision resulting from low flow states, thrombus formation, and position. In several instances, "down, up, down" patterns consisting of decreases in pH, increases in Pco2 , and decreases in Po2 were found to be associated with thrombus formation at the probe tip. 14• 16 In vivo Po2 estimates appeared to be particularly sensitive to positioning within the artery. In humans, isolated decreases in Po2 were found to result when the sensor touches the arterial wall. 14• 15 The accuracy of the Po2 estimate could not be assured. Large standard errors in in vivo Po2 estimates correlated with the underestimation of arterial Po 2 • Changes in sensor configuration did not enhance performance, and the manufacturer withdrew from the in vivo market to pursue an ex vivo device that could match the accuracy of laboratory instruments. A prospective, multicenter trial of the ex vivo ABG monitoring system was reported by Shapiro and colleagues. 28 It demonstrated that FOCS-based technology can withstand the rigors of bedside conditions. The system studied does not perform as a blood gas monitor, however, because it requires an operator to aspirate blood into a sensor cassette for periodic ABG measurements. Alternative FOCS systems for blood gas monitoring have been designed for in vivo ABGs. Zimmerman and Dellinger36 reported on the performance of a FOCS system (Optex Biomedical, Woodlands, TX) in five patients. It performed reliably and demonstrated clinical accuracy similar to that of laboratory measurements. The PB 3300 blood gas monitor (Puritan-Bennett Corp, Carlsbad, CA) recently was introduced into clinical practice. Although this system has not completed a published multicentered trial, three preliminary reports suggest it has clinical utility and a clinical performance similar to stand-alone arterial blood gas analyzers. 8• 11 • 31 Interface problems for in vivo systems continue to be raised, particularly when gas tensions are high. Haller et al 11 found that the PB 3300 system accurately tracked the changes observed in patients with severe respiratory failure. FOCS systems appear to be stable and reliable. The FOCS sensor performs adequately when the wrist is properly positioned. As with pulse oximetry, the accuracy of information obtained during CIABG monitoring depends on maintaining radial arterial flow past the FOCS sensor. Table 6 compares the characteristics of the two designs. The Cardiovascular Devices Inc or CDI methodology has demonstrated performance criteria equivalent to laboratory instruments. The design does not meet the criteria for an ABG monitor in that its operation is not seamless. Bedside testing has been popularized as a more efficient means of
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Table 6. CHARACTERISTICS OF TWO FI BEROPTIC CHEMICAL SENSOR SYSTEMS Characteristic
Performance Operable with arterial line Dampening of trace Simultaneous blood pressure Biocompatible Minimize thrombosis Seamless operation Perform at low flows Thermal stability Monitoring functions Cost-effectiveness
COi 2000
PB 3300
Equal to ABGs Yes < 10% Yes
Not quite equal to ABGs Yes < 10% Yes
Yes Yes Requires perst>nnel Not a problem Not a problem Discontinuous Unproven
Yes Not reported to be problem Completely seamless May influence accuracy Not a problem Continuous Unproven
obtaining test results. 34 Point-of-care systems represent an attempt by instrument makers to miniaturize laboratory devices to make them portable and simple to operate. The CDI 2000 FOCS system is an example of a point-of-care blood gas analyzer. Miniaturized electrochemical sensors that can be plugged into portable instruments are under development. User-operated point-of-care instruments are available for clinical use (GEM-STAT; Mallinckrodt Sensor Systems, Ann Arbor, MI). Initial evaluation in children undergoing cardiac surgery suggests that electrochemical sensor cartridge systems can perform as well as laboratory instruments at the bedside. 18 Disposable, single-use cartridges containing ABG biosensors recently have been designed to simplify start-up and quality control. Transportable, battery-operated, point-of-care systems have been designed and tested in a variety of clinical environments (IRMA; Diametrics Medical Inc, Roseville, MN). Initial investigation suggests that these instruments may become promising alternatives to stat laboratories. 32 Figure 2 illustrates the size of the IRMA cartridge. Upon opening the sealed packaging, the IRMA cartridge is inserted into the control module and the electronics section automatically checks the functionality of the cartridge. Issues such as cost effectiveness and reliability are undergoing clinical study. The ideal blood gas monitor would provide continuous measurements, have programmable alarm limits, and have a seamless operation that avoids blood sampling and interface problems associated with being located within an arterial cannula. Point-of-care analysis offers two advantages over the traditional ABG laboratory: Point-of-care, irrespective of the technology employed, eliminates the influence of transport time on ABG analysis and interpretation, and may reduce therapeutic decision time.5 Furthermore, if the technology employed has a fast response time, it is possible that a point-of-care system can serve as a patient care monitor, enabling clinicians to titrate common therapeutic modalities designed for the restoration of cardiopulmonary homeostasis. Both FOCS systems and miniaturized electrochemical systems can
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Figure 2. Disposable cartridge for bed-side arterial blood gases. This photo demonstrates the size of the IRMA cartridge. The cartridge is packaged in a sealed container which sets the diagnostic section when connected to the electronic control module. The suitability of the cartridge is tested and a complete blood gas analysis can be performed in less than 2 minutes. (Courtesy of Diametrics Medical Inc., Roseville, MN)
achieve measurements that match the clinical performance of laboratory instruments. The simplicity of their designs and ease of maintenance make them attractive alternatives. If these systems have a cost benefit as well as their convenience benefit, they will become the standard methods for measuring ABGs in the future. References l. Andritsch RF, Mauravchick S, Gold MI: Temperature correction of arterial blood gas
parameters: A comparative review of methodology. Anesthesiology 55:311-316, 1981 2. Bageant RA: Variations in arterial blood gas measurements due to sampling techniques. Respiratory Care 20:565-570, 1975 3. Becker H, Vinten-Johansen J, Buckberg GD, et al: Myocardial damage caused by keeping pH 7.4 during deep systemic hypothermia. J Thorac Cardiovasc Surg 82:810820, 1981 4. Bongard FS, Leighton TA: Continuous dual oxirnetry in surgical critical care. Indications and limitations. Ann Surg 216:60-68, 1992 5. Chernow B: The bedside laboratory: A critical step forward in ICU care. Chest 97:1831845, 1990 6. Clinical Laboratory Improvement Amendments of 1988: Final Rule.M. Federal Register 57:7001-7288, 1992 7. Delaney CJ, Leary ET, Raisys VA, et al: Proficiency testing of blood-gas quality control. Clin Chern 22:1675-1684, 1976 8. Depoix JP, Desrnonts JM, Camus F, et al: Evaluation of a continuous blood gas monitor during open heart surgery. Anesthesiology 79:A563, 1993
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9. Eberhard P, Fehlmann W, Mindt W: An electrochemical sensor for continuous intravascular oxygen monitoring. Biotelemetry and Patient Monitoring 6:51-65, 1979 10. Gehrich JL, Lubbers OW, Opitz N, et al: Optical fluorescence and its application to an intravascular blood gas monitoring system. IEEE Trans Biomed Eng 33:117-132, 1986 11. Haller M. Kilger E, Briegel J, et al: Coninuous intra-arterial blood gas monitoring in patients with severe respiratory failure: A prospective, criterion standard study. Crit Care Med 22:580--587, 1994 12. Hansen JE, Jensen RL, Casaburi R, et al: Comparison of blood gas analyzer biases in measuring tonometered blood and a fluorocarbon-containing, proficiency-testing material. Am Rev Respir Dis 140:403-409, 1989 13. lnterlaboratory comparison program surveys manual, Section ill: Clinical Chemistry. Northfield, IL, College of American Pathologists, 1992, pp 28--29 14. Mahutte CK: On-line blood gas monitoring. ln Tobin MJ (ed): Contemporary Management in Critical Care. New York, Churchill Livingstone 1:28--46, 1991 15. Mahutte CK, Sassoon CSH, Muro JR, et al: Progress in the development of a fluorescent intravascular blood gas system in man. J Clin Monit 6:147-157, 1990 16. Miller WW, Yafuso M, Yan CF, et al: Performance of an in-vivo continuous blood gas monitor with disposable probe. Clin Chem 33:1538--1542, 1987 17. Nearman HS, Herman ML, Clay W, et al: A new technology for continuous intraarterial blood gas monitors. Anesthesiology 79:A565, 1993 18. Nicolson SC, Jobes DR, Steve JM: Evaluation of a user-operated patient-side blood gas and chemistry monitor in children undergoing cardiac surgery. J Cardiothorac Anesth 3:741-744, 1989 19. Peterson J IT, Fitzgerald RV, Buckhold DK: Fiber-optic probe for in vivo measure of oxygen partial pressure. Anal Chem 58:62--67, 1984 20. Pfeifer PM, Pearson OT, Clayton RH: Clinical trial of the Continucath intra-arterial oxygen monitor. Anaesthesia 43:677-682, 1988 21. Pino JH, Bashein G, Kenny AM: In vitro assessment of flow-through fluorometric blood gas monitor. J Clin Monit 4:186-194, 1988 22. Reeves RB: An imidazole alphastat hypothesis of vertebrate acid-base regulation: Tissue carbon dioxide and body temperature in bull frogs. Respir Physiol 14:219-236, 1972 23. Regnault WF, Picciolo GL: Review of medical biosensors and associated material problems. J Biomed Mater Res Appl Biomater 21:163- 180, 1987 24. Richman KA, Jobes DR, Schwalb AJ: Continuous in-vivo blood gas determination in man: Reliability and safety of a new device. Anesthesiology 52:313-317, 1980 25. Shapiro BA: Evaluation of blood gas monitors: Performance criteria, clinical impact, and cost/benefit. Crit Care Med 22:546-548, 1994 26. Shapiro BA, Cane RD: Progress in the development of a fluorescent intravascular blood gas system in man. JClin Monit 7:212, 1991 27. Shapiro BA, Cane RD, Chomka C, et al: Preliminary evaluation of an inter-arterial blood gas system in dogs and humans. Crit Care Med 17:455-460, 1989 28. Shapiro BA, Manutte CK, Can RD, et al: Clinical performance of a blood gas monitor: A prospective, multicenter trial. Crit Care Med 21:487-494, 1993 29. Shapiro BA, Peruzzi WT: Arterial blood gas monitoring. In Tobin MJ (ed): Contemporary management in critical care. New York, Churchill Livingstone, 1:20--25, 1991 30. Siggaard-Anderson 0, Wimberley PD, Fogh-Anderson N, et al: Arterial oxygen status determined with routine pH/blood gas equipment and multi-wavelength hemoximetry: Reference values, precision and accuracy. Scand JClin Lab Invest 50(suppl 203) :5766, 1990 31. Vender JS, Gilbert HC, O'Connor BS, et al: Validation of continuous blood gas monitoring (CIABG) in coronary artery patients. Anesthesiology 79:A564, 1993 32. Vender JS, Gilbert H, Kehoe T: Evaluation of a new point-of-care blood gas monitor. Crit Care Med 22:A24, 1994 33. Wickers EK, Tenunissen AJ, Van den Camp RA, et al: A comparative study of the electrode systems of three pH and blood gas apparatus. J Clin Chem Biochem 16:175-185, 1978
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34. Wong DK, Jordon WS: Microprocessor-based near real-time bedside blood chemistry monitor. Int J Clin Monit Comput 9:95-102, 1992 35. Yafuso M, Arick SA, Hansmann D, et al: Optical pH measurements in blood. Proc SPIE-Int Soc Opt Eng 1067:37-42, 1989 36. Zimmerman JL, Dellinger RP: Initial evaluation of a new intra-arterial blood gas system in humans. Crit Care Med 21:495-500, 1993 Address reprint requests to
Hugh C. Gilbert, MD Division of Anesthesiology Evanston Hospital 2650 Ridge A venue Evanston, IL 60201
.....
0749-0704/95 $0.00 + .20
ARTERIAL BLOOD GAS MONITORING Hugh C. Gilbert, MD, and Jeffery S. Vender, MD, FCCM
Blood gas determinations (ABGs) play an important role in diagnosing potentially life-threatening derangements in acid-base balance, oxygenation, and ventilation. Managing critically ill patients requires frequent assessment of ABGs. This article reviews the technologic evolution of modern blood gas analysis and the clinical application of monitoring hydrogen ion content (pH), blood oxygen tension (Po2 ), and carbon dioxide tension (Pco 2). For many years, ABGs have been performed in specialized laboratories. Prior to the development of the modern acid-base laboratory (defined as integrated equipment that measures "blood gases"), monitoring cardiopulmonary homeostasis was difficult. Until the development of electrochemical sensors, clinicians were unable to assess ABGs routinely. Manometric and volumetric determinations of the "gas" content of blood were available in specialized areas of the hospital but the equipment was too cumbersome and impractical to be considered for monitoring critically ill patients. Table 1 illustrates the chronology of ABGs to the development of electrochemical sensors. During the past 20 years, the most significant advance in in vitro blood gas analysis has been due to the miniaturization and automation of microprocessorcontrolled instruments that simplify the process of blood gas measurements. The components of a modern blood gas machine include: 1. a gas mixer that produces calibrating gases containing known
partial pressures of 0 2 and C0 2; 2. a measurement section that contains valves, tubing, pumps, and From the Department of Anesthesiology (HCG, JSV), Northwestern University Medical School, Chicago; Medical-Surgical Intensive Care Unit GSV); and Division of Anesthesiology (HCG, JSV), Evanston Hospital, Evanston, Illinois
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Table 1. THE CHRONOLOGY OF THE BLOOD GAS LABORATORY Date
< 1950 1957 1957 1958 1970
Development Gas analysis Sanz electrode Stow electrode Severinghaus electrode IL co-oximeter
Methodology
Measurement
Volumetric Mano metric Electrochemical Electrochemical Electrochemical Spectrophotometric
Oxygen content Carbon dioxide content pH Pco2 Pco2 Hbo2, Hbco
Pco2 = carbon dioxide tension ; Hbo2 = hemoglobin oxygen content; Hbco = hemoglobin carbon monoxide.
heaters that transport the sample under controlled conditions to an electrode bank where the measurements are made; 3. a rinsing section containing the maintenance solutions that refresh the electrode bank following each measurement; and 4. an electronics section that monitors the other components, controls the movement of gases and liquids, initiates calibrations, performs diagnostic tests, and prints a report of the analysis and status of all instrument functions. Instruments of this description have been available for clinical practice for 20 years. Today's automated blood gas analyzers use specialized electrochemical sensors for measuring pH, Pco 2, and Po2 • The pH and Pco 2 electrodes quantify the difference in pH between two solutions using an electrolytic circuit. At 37°C, a properly functioning pH electrode will register a 61.5 m V change for each pH unit difference between a known buffer solution and the unknown blood sample. The voltage change can be calculated by a modification of the Nernst equation. The Pco2 electrode uses the same design concept as that for pH. A typical Pco2 electrode contains a pH electrode that is separated from the blood sample by a C0 2 permeable membrane. A buffer solution of sodium bicarbonate (NaHC03 ) and sodium chloride (NaCl) resides on the sample side of the pH electrode. As the C0 2 gas crosses the membrane, the pH of the buffer changes in proportion to the partial pressure of C02 crossing the membrane. Most blood gas analyzers contain a Clark electrode for measuring the partial pressure of oxygen. The Po2 electrode is based on the oxidation-reduction reaction of dissolved oxygen and water. The reaction requires a constant supply of electrons, which are provided by a polarizing voltage applied to a silver wire. For this reason, the Clark electrode also is called a polarographic electrode. An oxygen-permeable membrane isolates the electrode system, reducing the effect of plasma proteins on the reaction. At a platinum cathode, oxygen combines with four electrons. Under these circumstances, the electrode current depends on the reduction of oxygen at the platinum electrode: I = S x Po2 + Io, where S is the sensitivity and Io is the current when Po2 = 0. These three electrodes represent the basic components used to measure ABGs. Modern blood gas analyzers initiate calibration sequences
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automatically at preprogrammed intervals. During calibration, the estimated value for the analyte of interest is compared with a theoretical value based on the measured barometric pressure and the calculated value of the partial pressure of the calibrating gas mixture. The performance of a blood gas analyzer must be evaluated periodically to ensure that the estimates are accurate.7 ERRORS OF ANALYSIS AND PERFQRMANCE CRITERIA
Laboratory instruments must comply with three performance criteria: Accuracy defines the nearness of a measurement to the actual value of the variable being measured, bias represents a consistent difference of the variable, and precision defines the closeness of the measurement. 25 The electrochemical sensors employed in blood gas analyzers are expected to have a high degree of precision. Wickers et al compared the precision of three common systems;33 Table 2 lists the laboratory precision observed in this study for electrochemical sensors measuring known analytes in a short time frame. Electrochemical sensors drift over time. Modern instruments perform single point calibration to stabilize electrode performance, reducing the importance of drift as a source of inaccuracy. Blood gas laboratories are required to enroll in proficiency testing.7 One such program is operated by the American Thoracic Society (ATS). ATS testing uses a fluorocarbon emulsion that serves as an artificial blood control. Samples are sent to participating laboratories and the results from the participating laboratories are compared. An instrument report is generated for each laboratory and a rating is assigned based on the statistical analysis of the ranges of values submitted by the participants. Proficiency testing documents the bias of blood gas instruments and their operators. Testing programs ensure clinicians that ABG measurements have an acceptable accuracy and precision.7 Inter- and intrainstrument variability is expected to occur within prescribed boundaries. Table 3 lists the proficiency limits accepted by the College of American Pathologists and the Health Care Financing Administration. 6• 13 Stand-alone instruments have an advantage over in vivo or in continuity instruments because it is always possible to assess clinical performance and sensor drift during the period of clinical usage by performing Table 2. PRECISION OF ELECTROCHEMICAL SENSORS Electrode
Measurement
Sanz Severinghaus
pH Pco2
± 0.01 pH unit ± 2%
Clark
Po2
± 1 mm Hg at 40 mm Hg ± 3% ± 2.5 mm Hg at 80 mm Hg
Precision
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Table 3. PROFICIENCY TESTING LIMITS FOR BLOOD GAS LABORATORIES* Parameter
CAP Limits
HCFA Limits
pH PC02 Po2
± 0.03 ± 3 mmHg ± 7.5%
± 0.04 ± 5 mmHg ± 3 SD
CAP = College of American Pathologists; HCFA = Health Care Financing Administration ; Pco, = carbon dioxide tension ; Po, = blood oxygen tension. pH is reported in pH units. SD refers to the standard deviation of the proficlency testing group. ·A blood gas laboratory refers to the instrument and its operator. From Shapiro BA: Evaluation of blood gas monitors: Performance criteria, clinical impact, and cost/ benefit. Grit Care Med 22:546-548, 1994; with permission.
periodic calibrations. In vivo sensors are designed to be calibrated prior to their insertion. Other factors can influence the accuracy of an ABG measurement or its clinical interpretation. TEMPERATURE CORRECTION
Temperature correction represents the most important physical factor that may influence clinical interpretation of ABGs. The effects of temperature and pressure are operational for all methodologies currently employed for measuring ABGs. Blood gas analysis is carried out at 37°C. Temperature influences gas solubility, ion dissociation, and the offloading of oxygen from hemoglobin. As a general guideline, Po2 and Pco2 decrease (ideal gas law) and pH increases when temperature falls below 37°C. Table 4 lists the changes of the ABG analytes as a function of temperature. Temperature correction may be of clinical importance in patients whose temperatures are outside the range of 35° to 39°C. Blood gas analyzers report the results of analysis corrected to 37°C. Most analyzers can report their results at any patient temperature. Table 4. THE EFFECT OF TEMPERATURE ON pH , CARBON DIOXIDE TENSION , AND BLOOD OXYGEN TENSION MEASUREMENTS Temperature
oc
OF
pH
Pco.
Po 2
20 30 35 36 37 38 40
68 86 95 97 98 100 104
7.65 7.50 7.43 7.41 7.40 7.39 7.36
19 30 37 38 40 42 45
27 51 70 75 80 85 97
Pco, = carbon dioxide tension; Po, = blood oxygen tension . From Shapiro, Peruzzi , Kozelowski-Templin: Clinical Application of Blood Gases, ed 5. St. Louis, Mosby-Year Book, 1994, p 128; with permission .
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The clinical importance of temperature correction versus reporting the results at the patient's measured temperature is still hotly debated. Clinicians who use uncorrected ABGs subscribe to the concept of alpha stat interpretation. Alpha refers to the histidine imidazole locus on hemoglobin, which plays a central role in the ability of hemoglobin to buffer pH changes during oxygen transport. In vitro studies suggest that, following cooling, the pH of amphibian blood behaves in a manner similar to that of aqueous solutions containing carbonic acid, bicarbonate (HC0 3), and imidazole. 22 Poikilothermi~ species do not correct their pH during cooling. On the other hand, hibernating animals maintain their blood pH during cooling by increasing their C02 content. The strategy whereby C0 2 is added to maintain pH during deep hypothermia is based on the premise that hypothermic humans should behave in the same way as hibernating species. This management plan has been termed pH stat. Animal studies indicate that pH stat management often results in excessive alkalemia when hypothermic animals are administered NaHC0 3 to correct the "normalized pH" during rewarming.3 pH Stat management has been associated with depressed myocardial contractility during rewarming. On the other hand, pH stat proponents believe that cerebral perfusion is preserved best by normalizing pH during hypothermia. Altering temperature affects the solubility of oxygen as well as hemoglobin's affinity for oxygen. Changing blood temperature will influence the Po 2 but does not change the measured oxygen content. In response to a decreasing temperature, hemoglobin increases its affinity for oxygen (a leftward shift of the oxyhemoglobin dissociation curve), resulting in a decrease in oxygen tension. Conversely, increasing temperature decreases the affinity of hemoglobin for oxygen, resulting in enhanced off-loading and an increase in Po2 • The importance of this temperature effect is demonstrated in Table 4, in which an arterial blood sample at 30°C has a measured Po2 of 51 mm Hg, equivalent to measuring 80 mm Hg at 37°C. Oxygenation is best evaluated at the standard 37°C values because the actual temperature is rarely determined at the time of sampling. The effect of fluctuating temperature on metabolism, vascular function, and respiration in critically ill patients is complex. Blood gas measurements use standard conditions (known as BTPS), in which 37°C represents the standard normal body temperature and pressure represents the atmospheric pressure to which the body is exposed fully saturated with water.1
ARTERIAL BLOOD GAS SAMPLING
Until recently, ABGs required intermittent blood gas sampling, using either an indwelling arterial cannula or direct arterial puncture. In critically ill patients, it is common to require frequent sampling to monitor ABG derangements and their response to therapy. Blood gas samples are susceptible to sampling errors.2 Until the introduction of
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point-of-care and in vivo methodologies, ABC analysis required obtaining a blood sample and transporting it to the location where analysis occurred. Historically, issues such as the composition of syringe, the chemistry of the anticoagulant, and the conditions used for transport have been raised and evaluated. Although plastic syringes may absorb oxygen at partial pressures above 400 mm Hg, they are in common use. Today, heparin is the anticoagulant of choice. Most heparins have a pH of approximately 7. Clinicians and their support staff have been trained to reduce the potential of introducing sampling errors when obtaining ABCs. Blood samples must be obtained under strict anaerobic conditions and be placed on ice and held at 0°C until analysis. Air bubbles interfere with the accuracy of gas analysis. Contamination with room air raises the estimate of the Po2 and lowers the Pco2 when sampled from normal subjects breathing room air. The effect of room air contamination (Po2 = 150; Pco2 = 0) depends on the physiologic conditions present at the time of sampling and oxygen delivery. Icing the sample eliminates the influence of metabolically active white cells present in the sample. Spontaneous changes in oxygen consumption, cardiac output, and the systemic distribution of blood flow have been implicated as factors that may influence the variability of ABC values observed in clinically stable patients who have undergone frequent blood gas sampling.
INSTRUMENT VARIABILITY
The issue of the analysis and interpretation of blood gas instrument similarities and differences is complex. Of the analytes in question, the Po2 value often is disparate when comparing a sample analyzed on different instruments. Hansen and colleagues 12 compared the biases of six models of blood gas instruments in common usage. Their studies demonstrate that instrument variation is quite common and quality control analytes tend to overestimate instrument bias compared with tonometered blood. 12
THE VALUE OF BLOOD GASES
Accurate knowledge of pH, Pco2 , Po2 , and total hemoglobin in both arterial and pulmonary blood has been very helpful in clinical decision making. Indices such as oxygen content (Cao2), HC03, base excess, and oxyhemoglobin saturation can be derived mathematically from ABC analysis. Parameters such as arterio-venous oxygen content differences (C(a-v)o2 ) and intrapulmonary shunt can be calculated from arterial and venous gas analysis. These factors play an important role in evaluating overall cardiopulmonary function and tissue oxygenation. When ABC analysis is combined with multiwavelength oximetry, active hemoglobin concentration, total oxygen concentration, actual half-satura-
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tion tension, and 2,3-diphosphoglycerate concentration can be estimated mathematically. 30 This suggests that routine ABGs and multiwavelength oximetry contain significant information concerning the oxygen status of patients. In critical care units, monitoring arterial oxygenation is a clinical imperative. The maintenance of cellular oxygenation depends on an effective cardiac output (CO), perfusion, and arterial Cao2 • Cao2 is calculated using the following formula: Cao2 = (Pao2
X
0.003)
+ Hb
X
Sao2
X
1.34) vol %,
where Hb is hemoglobin and Sao 2 is arterial oxygen percent saturation. The capability of critically ill patients to maintain tissue oxygenation is quantified by calculating oxygen delivery (00 2 ): 002
=
Cao2 x CO
The information gained by monitoring cardiovascular and metabolic influences on tissue oxygen balance is enhanced by calculating the oxygen content of both arterial and mixed-venous blood. Healthy patients have an oxygen content difference, C(a-v)o2 , of 5 vol %. Critically ill patients frequently have derangements in cardiac performance associated with increasing tissue oxygen demands, which may result in a decrease in C(a-v)o2 • Dual oximetry (using methods to monitor Sao2 and Svo2 continuously) has been proposed to be helpful in monitoring critically ill patients.4 Inadequate Do 2 or inadequate tissue perfusion results in tissue hypoxia and the development of lactic acidemia. Blood pH is essentially determined by the HC0 3 / carbonic acid relationship, the interplay of alterations in Pco 2 (ventilatory changes), and a metabolic component defined by the variance from the normal buffer base related to alterations in normal homeostasis. Clinically important acidemia is potentially life-threatening because of disturbances in essential enzyme systems and electrolyte balance. Autonomic receptors also are affected and the responses of exogenous drugs on receptor activation become unreliable. The interplay of the factors just mentioned defines the importance of ABG analysis in the clinical assessment of critically ill patients. 29 Po 2 Analysis is necessary to determine the presence or extent of hypoxernia, helps define the off-loading and uptake of oxygen by hemoglobin, and is essential in calculating oxygen delivery to the tissues. Po2 Analysis is essential for differentiation of pulmonary and cardiovascular factors that contribute to hypoxemia. Calculation of alveolar-to-arterial oxygen tension (P(A - a)o2 ) has important historical considerations as an index for quantifying disturbances in pulmonary oxygen transfer. Calculation of the shunt fraction has displaced the A - a gradient because it is more reliable in acutely ill patients. Shunt fraction requires pulmonary artery catheterization and measuring arterial and venous oxygen tensions. Blood pH measurement defines the presence or absence of acidernia or alkalernia. Ventilatory homeostasis is determined by assessment of
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the pH and Pco2. Inadequate alveolar ventilation is defined by the failure of ventilation to satisfactorily meet the demands of C02 excretion. C02 homeostasis in the critically ill is complicated by ongoing alterations in C02 production as well as peripheral stores. Compensated states frequently are encountered, in which pH is apparently normal, but significant increases are seen in peripheral and central C02 stores. Critically ill patients frequently demonstrate increases in dead space ventilation (V 0 ). V0 often is found in patients with cardiac failure, pulmonary embolus, pulmonary hypertension, and acute lung injury. Physiologic dead space is expresseo as a ratio of dead space-to-tidal volume (VT) and is calculated from the Bohr equation, where: Vo/ VT = (PaC02 - PEC02) I PaC02 PEC02 is expired C02. C02 homeostasis in the critically ill may be complex because C02 production and C02 peripheral stores may be abnormal. C02 production is increased approximately 10% per degree centrigrade rise in temperature. Shivering, rigor, or frank seizures can affect C02 production as well as oxygen consumption. Patients with head injuries or other central nervous system insults may demonstrate acute alveolar hyperventilation, resulting in depletion of central and peripheral C02 stores. Chronic hypercarbia also is multifactorial. Factors such as chronic obstructive pulmonary diseases, heredity, central chemoreceptor unresponsiveness to C02, and diminished myocardial reserves have been demonstrated to affect Pco2 and acid- base balance. ABC analysis therefore has a central place in the integration of pulmonary and cardiovascular homeostasis in critical care medicine. Monitoring represents the process by which clinicians recognize and evaluate dynamic physiologic processes in a timely manner. The term is derived from monere, which means to warn, remind, or admonish. The goal of ABC monitoring is to enhance clinical judgments regarding pulmonary and cardiovascular homeostasis by identifying changes in pH, Pco2, Po2, and all their derived parameters, almost continuously. Blood gas analyzers require the removal of blood and cannot be thought of as patient monitors unless they are dedicated to a specific patient and analysis is performed minute by minute. Blood gas analyzers can be miniaturized so they can become point-of-care instruments. Frequent use of point-of-care instruments can provide updates of ABCs and reduce the time between analysis and therapy. In this article, the term ABG monitor infers that the instrumentation is dedicated to a particular patient; updates the variables of interest at clinically appropriate intervals, automatically; can graphically trend pH, Pco2, and Po2; and operates without permanently removing blood from the patient. ABC monitoring presumes all the inherent risks and benefits of arterial cannulation. Table 5 summarizes some of the design constraints inherent in developing clinically useful ABC monitors. An ideal ABC monitor would provide continuous measurements, allowing for setting of alarm limits that alert the intensive care unit management team to initiate proactive
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Table 5. DESIGN CONSTRAINTS FOR BLOOD GAS MONITORS Have accuracy and performance comparable to ABG analyzers Be operable with a 20-gauge arterial catheter Permit simultaneous and continuous arterial pressure monitoring Must be biocompatible with blood Minimize the potential for thrombosis Be capable of seamless operation in an intensive care unit environment
Have a useful period of operation (72hour minimum) Perform accurately at low arterial blood flow Have thermal stability Be cost-effective
therapeutic interventions faster than is commonly achievable using blood gas analyzers. Several methodologies for estimating arterial blood gases have been adapted to develop instruments that can determine blood gases in vivo. In 1980, Richman and colleagues24 reported on using a specialized arterial probe and a portable gas chromatograph to continuously monitor ABG analytes. The probe was 15.2-cm long and had an external diameter of 0.07 cm. The technology did not meet the design characteristics necessary for in vivo monitoring because the system did not incorporate pH, the probe was cumbersome and large, vascular occlusion occurred, and the estimates of arterial oxygen pressure (Pao2 ) were affected by nitrous oxide. Gas transfer techniques (chromatography or mass spectrometry) do not appear to meet the criteria for clinical practice. Currently, there is no significant ongoing attempt to develop continuous, intra-arterial blood gas monitors (CIABGMs) based on gas transfer technology. On the other hand, systems using fiberoptics have undergone extensive investigation. 10 Glass or plastic fibers are ideal cables for indwelling sensing systems. They are isolated electrically and transport light by the phenomenon of total internal reflection. Measurements depend on the interaction of light with an indicator complex. To measure in vivo ABGs using fiberoptics, fiberoptic sensors for pH, Pco2 , Po2 , and a means to measure temperature (usually a thermocouple) must be designed to fit within a 20-gauge arterial cannula. A fiberoptic sensor system should allow continuous blood pressure monitoring, permit the intermittent sampling of blood for other analytes, and perform accurately without causing any increase in the risk of thrombosis within the artery or cannula for a period of 72 hours of usage in order to be a feasible replacement of current methods of surveying ABGs. 27 The following is a brief review of the scientific basis for fiberoptic measurement of ABGs. Light can be transmitted through optical fibers and is either absorbed or reflected. If the light is transmitted to an optically sensitive dye, the indicator may react with the light. Two reactions are possible. The indicator may change the character of the light by absorption, or the indicator can change the character of the light by becoming stimulated to fluoresce . Most fiberoptic systems designed for measuring ABGs use oxygen- and pH-sensitive dyes in their sensors.
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In a fluorescence-based sensor (Po2 ), an excitation signal (fluorescence) returns through the fiber. For oxygen, the intensity of this signal is inversely proportional to the concentration of oxygen in the arterial stream. Oxygen "quenches" the intensity of the fluorescence of the Po2 sensor dye. The intensity of the fluorescence therefore is least when oxygen tension is highest. Systems using oxygen quenching experience signal-noise disturbances at high oxygen tension. Absorbance-based sensors (pH, Pco2 ) transmit incident light to a dye cell.35 The dye absorbs the incident light based on the concentration of the analyte in question and the instrument measures the intensity of the light ·transmitted back through an optical transmission fiber. In a manner similar to that of the Severinghaus electrode, Pco 2 sensors incorporate an intermediate buffer layer between the blood interface and an optical pH-sensitive dye. Figure lA and B graphically depict the
Incident light
Dye cell
Transmitted light
--._/-~
- -··- A
Return (re-emitted) light signal
Dye
Excitation light signal
Figure 1. A, Diagram of an absorbance-based optical sensor. Absorbance-based optical sensors send light through the fiber to a dye cell. At the dye cell , the incident light is absorbed by the dye matrix. This degree of absorbance is a function of the concentration of the analyte of interest. The intensity of the returning unabsorbed light is proportional to the concentration of the analyte of interest. (Courtesy of the Puritan-Bennett Corporation, Carlsbad, CA) 8 , Diagram of a fluorescence-based optical sensor. Fluorescence-based optical sensors transmit an excitation light energy down the fiber. The dye at the tip reacts to the excitation light by fluorescing . The concentration of the analyte of interest influences the intensity of the fluorescence . The fluorescent signal then returns in the same fiber to the monitor, which measures the returning fluorescent signal. (Courtesy of the PuritanBennett Corporation, Carlsbad, CA)
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methodologies used in optical blood gas instruments. Absorbance-based sensors are similar to spectrophotometric laboratory devices in common use. Intravascular monitoring has posed major challenges to instrument designers. Electrochemical sensors have been designed to accommodate the size constraint. Microelectrodes (MEs) require electrical connections. Issues such as drift, intravascular fouling of surfaces, wire breakage, current leakage, and corrosion are significant constraints for the development of a clinically useful electroche~ical, in vivo, ABG monitor. Because the conditions of the measurement environment cannot be controlled intravascularly, microelecrodes must remain stable following calibration and insertion. Investigational devices have been designed and preliminary data on their performance characteristics have been reported. Eberhard et al 9 reported on the development of an ME for intravascular monitoring of oxygen. In 1988, Pfeifer, Pearson, and Clayton20 published their experience with an intra-arterial oxygen electrode in nine patients undergoing cardiac surgery. This report demonstrated that MEs for monitoring Po2 can perform well for short periods of time (> 26 hours). MEs having diameters approaching 2 µ,m have been designed for measuring cellular pH. Likewise, Pco2 MEs are feasible technically. Nearman and colleagues17 studied a Po2-Pco2 indwelling ME that uses miniature noble metal electrodes housed in chambers isolated by a biocompatible membrane. The system appears to have performance characteristics similar to fiberoptic sensors but has the advantage of lower production costs. A current version monitors pH, Pco2, and Po2. Fiberoptic chemical sensors (FOCS) are ideally suited to the intravascular environment. 19• 21 Reagents can be embedded in a matrix or encapsulated and bonded to the sensor probe. Optical fiber performance can be improved by coatings that enhance performance, strength, and blood compatibility. These membranes confine excitation and signal emissions, reducing optical noise resulting from naturally fluorescent molecules present at the probe-blood interface. FOCS probes may have a size advantage over MEs, making it possible to bundle several together for placement within arterial catheters. Electrical isolation also is a very desirable characteristic. FOCS-based systems have been designed for continuous intravascular applications. The first application was the design of ex vivo blood probes for monitoring ABGs in extracorporeal tubing. 20 These instruments were the first to demonstrate the benefits of continuous ABG monitoring. Although first-generation models did not perform as well as blood gas instruments, over time, these devices have become part of the standard extracorporeal set-up in many centers. The same FOCS system was modified to permit continuous, intravascular monitoring of ABGs. Bench studies of the intravascular system (CDI-1000, CDI-3M Healthcare, Irving, CA) using heparinized bovine blood demonstrated good correlation with standard measurements. Animal studies also were encouraging. The probe's performance warranted
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further study. The in vivo FOCS monitored physiologic changes in blood gas values as they occurred and was not adversely influenced by commonly infused drugs or anesthetic agents.15• 16 Preliminary evaluations in human subjects demonstrated that in vivo FOCS could identify changes in ABGs as they occur and significantly reduce the lag time for interpretation, to approximately 3 minutes. Comparison data suggest that Pco2 and pH estimates are virtually equivalent to standard laboratory estimates. The investigators of early FOCS systems were concerned with the potential for imprecision resulting from low flow states, thrombus formation, and position. In several instances, "down, up, down" patterns consisting of decreases in pH, increases in Pco2 , and decreases in Po2 were found to be associated with thrombus formation at the probe tip. 14• 16 In vivo Po2 estimates appeared to be particularly sensitive to positioning within the artery. In humans, isolated decreases in Po2 were found to result when the sensor touches the arterial wall. 14• 15 The accuracy of the Po2 estimate could not be assured. Large standard errors in in vivo Po2 estimates correlated with the underestimation of arterial Po 2 • Changes in sensor configuration did not enhance performance, and the manufacturer withdrew from the in vivo market to pursue an ex vivo device that could match the accuracy of laboratory instruments. A prospective, multicenter trial of the ex vivo ABG monitoring system was reported by Shapiro and colleagues. 28 It demonstrated that FOCS-based technology can withstand the rigors of bedside conditions. The system studied does not perform as a blood gas monitor, however, because it requires an operator to aspirate blood into a sensor cassette for periodic ABG measurements. Alternative FOCS systems for blood gas monitoring have been designed for in vivo ABGs. Zimmerman and Dellinger36 reported on the performance of a FOCS system (Optex Biomedical, Woodlands, TX) in five patients. It performed reliably and demonstrated clinical accuracy similar to that of laboratory measurements. The PB 3300 blood gas monitor (Puritan-Bennett Corp, Carlsbad, CA) recently was introduced into clinical practice. Although this system has not completed a published multicentered trial, three preliminary reports suggest it has clinical utility and a clinical performance similar to stand-alone arterial blood gas analyzers. 8• 11 • 31 Interface problems for in vivo systems continue to be raised, particularly when gas tensions are high. Haller et al 11 found that the PB 3300 system accurately tracked the changes observed in patients with severe respiratory failure. FOCS systems appear to be stable and reliable. The FOCS sensor performs adequately when the wrist is properly positioned. As with pulse oximetry, the accuracy of information obtained during CIABG monitoring depends on maintaining radial arterial flow past the FOCS sensor. Table 6 compares the characteristics of the two designs. The Cardiovascular Devices Inc or CDI methodology has demonstrated performance criteria equivalent to laboratory instruments. The design does not meet the criteria for an ABG monitor in that its operation is not seamless. Bedside testing has been popularized as a more efficient means of
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Table 6. CHARACTERISTICS OF TWO FI BEROPTIC CHEMICAL SENSOR SYSTEMS Characteristic
Performance Operable with arterial line Dampening of trace Simultaneous blood pressure Biocompatible Minimize thrombosis Seamless operation Perform at low flows Thermal stability Monitoring functions Cost-effectiveness
COi 2000
PB 3300
Equal to ABGs Yes < 10% Yes
Not quite equal to ABGs Yes < 10% Yes
Yes Yes Requires perst>nnel Not a problem Not a problem Discontinuous Unproven
Yes Not reported to be problem Completely seamless May influence accuracy Not a problem Continuous Unproven
obtaining test results. 34 Point-of-care systems represent an attempt by instrument makers to miniaturize laboratory devices to make them portable and simple to operate. The CDI 2000 FOCS system is an example of a point-of-care blood gas analyzer. Miniaturized electrochemical sensors that can be plugged into portable instruments are under development. User-operated point-of-care instruments are available for clinical use (GEM-STAT; Mallinckrodt Sensor Systems, Ann Arbor, MI). Initial evaluation in children undergoing cardiac surgery suggests that electrochemical sensor cartridge systems can perform as well as laboratory instruments at the bedside. 18 Disposable, single-use cartridges containing ABG biosensors recently have been designed to simplify start-up and quality control. Transportable, battery-operated, point-of-care systems have been designed and tested in a variety of clinical environments (IRMA; Diametrics Medical Inc, Roseville, MN). Initial investigation suggests that these instruments may become promising alternatives to stat laboratories. 32 Figure 2 illustrates the size of the IRMA cartridge. Upon opening the sealed packaging, the IRMA cartridge is inserted into the control module and the electronics section automatically checks the functionality of the cartridge. Issues such as cost effectiveness and reliability are undergoing clinical study. The ideal blood gas monitor would provide continuous measurements, have programmable alarm limits, and have a seamless operation that avoids blood sampling and interface problems associated with being located within an arterial cannula. Point-of-care analysis offers two advantages over the traditional ABG laboratory: Point-of-care, irrespective of the technology employed, eliminates the influence of transport time on ABG analysis and interpretation, and may reduce therapeutic decision time.5 Furthermore, if the technology employed has a fast response time, it is possible that a point-of-care system can serve as a patient care monitor, enabling clinicians to titrate common therapeutic modalities designed for the restoration of cardiopulmonary homeostasis. Both FOCS systems and miniaturized electrochemical systems can
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Figure 2. Disposable cartridge for bed-side arterial blood gases. This photo demonstrates the size of the IRMA cartridge. The cartridge is packaged in a sealed container which sets the diagnostic section when connected to the electronic control module. The suitability of the cartridge is tested and a complete blood gas analysis can be performed in less than 2 minutes. (Courtesy of Diametrics Medical Inc., Roseville, MN)
achieve measurements that match the clinical performance of laboratory instruments. The simplicity of their designs and ease of maintenance make them attractive alternatives. If these systems have a cost benefit as well as their convenience benefit, they will become the standard methods for measuring ABGs in the future. References l. Andritsch RF, Mauravchick S, Gold MI: Temperature correction of arterial blood gas
parameters: A comparative review of methodology. Anesthesiology 55:311-316, 1981 2. Bageant RA: Variations in arterial blood gas measurements due to sampling techniques. Respiratory Care 20:565-570, 1975 3. Becker H, Vinten-Johansen J, Buckberg GD, et al: Myocardial damage caused by keeping pH 7.4 during deep systemic hypothermia. J Thorac Cardiovasc Surg 82:810820, 1981 4. Bongard FS, Leighton TA: Continuous dual oxirnetry in surgical critical care. Indications and limitations. Ann Surg 216:60-68, 1992 5. Chernow B: The bedside laboratory: A critical step forward in ICU care. Chest 97:1831845, 1990 6. Clinical Laboratory Improvement Amendments of 1988: Final Rule.M. Federal Register 57:7001-7288, 1992 7. Delaney CJ, Leary ET, Raisys VA, et al: Proficiency testing of blood-gas quality control. Clin Chern 22:1675-1684, 1976 8. Depoix JP, Desrnonts JM, Camus F, et al: Evaluation of a continuous blood gas monitor during open heart surgery. Anesthesiology 79:A563, 1993
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9. Eberhard P, Fehlmann W, Mindt W: An electrochemical sensor for continuous intravascular oxygen monitoring. Biotelemetry and Patient Monitoring 6:51-65, 1979 10. Gehrich JL, Lubbers OW, Opitz N, et al: Optical fluorescence and its application to an intravascular blood gas monitoring system. IEEE Trans Biomed Eng 33:117-132, 1986 11. Haller M. Kilger E, Briegel J, et al: Coninuous intra-arterial blood gas monitoring in patients with severe respiratory failure: A prospective, criterion standard study. Crit Care Med 22:580--587, 1994 12. Hansen JE, Jensen RL, Casaburi R, et al: Comparison of blood gas analyzer biases in measuring tonometered blood and a fluorocarbon-containing, proficiency-testing material. Am Rev Respir Dis 140:403-409, 1989 13. lnterlaboratory comparison program surveys manual, Section ill: Clinical Chemistry. Northfield, IL, College of American Pathologists, 1992, pp 28--29 14. Mahutte CK: On-line blood gas monitoring. ln Tobin MJ (ed): Contemporary Management in Critical Care. New York, Churchill Livingstone 1:28--46, 1991 15. Mahutte CK, Sassoon CSH, Muro JR, et al: Progress in the development of a fluorescent intravascular blood gas system in man. J Clin Monit 6:147-157, 1990 16. Miller WW, Yafuso M, Yan CF, et al: Performance of an in-vivo continuous blood gas monitor with disposable probe. Clin Chem 33:1538--1542, 1987 17. Nearman HS, Herman ML, Clay W, et al: A new technology for continuous intraarterial blood gas monitors. Anesthesiology 79:A565, 1993 18. Nicolson SC, Jobes DR, Steve JM: Evaluation of a user-operated patient-side blood gas and chemistry monitor in children undergoing cardiac surgery. J Cardiothorac Anesth 3:741-744, 1989 19. Peterson J IT, Fitzgerald RV, Buckhold DK: Fiber-optic probe for in vivo measure of oxygen partial pressure. Anal Chem 58:62--67, 1984 20. Pfeifer PM, Pearson OT, Clayton RH: Clinical trial of the Continucath intra-arterial oxygen monitor. Anaesthesia 43:677-682, 1988 21. Pino JH, Bashein G, Kenny AM: In vitro assessment of flow-through fluorometric blood gas monitor. J Clin Monit 4:186-194, 1988 22. Reeves RB: An imidazole alphastat hypothesis of vertebrate acid-base regulation: Tissue carbon dioxide and body temperature in bull frogs. Respir Physiol 14:219-236, 1972 23. Regnault WF, Picciolo GL: Review of medical biosensors and associated material problems. J Biomed Mater Res Appl Biomater 21:163- 180, 1987 24. Richman KA, Jobes DR, Schwalb AJ: Continuous in-vivo blood gas determination in man: Reliability and safety of a new device. Anesthesiology 52:313-317, 1980 25. Shapiro BA: Evaluation of blood gas monitors: Performance criteria, clinical impact, and cost/benefit. Crit Care Med 22:546-548, 1994 26. Shapiro BA, Cane RD: Progress in the development of a fluorescent intravascular blood gas system in man. JClin Monit 7:212, 1991 27. Shapiro BA, Cane RD, Chomka C, et al: Preliminary evaluation of an inter-arterial blood gas system in dogs and humans. Crit Care Med 17:455-460, 1989 28. Shapiro BA, Manutte CK, Can RD, et al: Clinical performance of a blood gas monitor: A prospective, multicenter trial. Crit Care Med 21:487-494, 1993 29. Shapiro BA, Peruzzi WT: Arterial blood gas monitoring. In Tobin MJ (ed): Contemporary management in critical care. New York, Churchill Livingstone, 1:20--25, 1991 30. Siggaard-Anderson 0, Wimberley PD, Fogh-Anderson N, et al: Arterial oxygen status determined with routine pH/blood gas equipment and multi-wavelength hemoximetry: Reference values, precision and accuracy. Scand JClin Lab Invest 50(suppl 203) :5766, 1990 31. Vender JS, Gilbert HC, O'Connor BS, et al: Validation of continuous blood gas monitoring (CIABG) in coronary artery patients. Anesthesiology 79:A564, 1993 32. Vender JS, Gilbert H, Kehoe T: Evaluation of a new point-of-care blood gas monitor. Crit Care Med 22:A24, 1994 33. Wickers EK, Tenunissen AJ, Van den Camp RA, et al: A comparative study of the electrode systems of three pH and blood gas apparatus. J Clin Chem Biochem 16:175-185, 1978
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34. Wong DK, Jordon WS: Microprocessor-based near real-time bedside blood chemistry monitor. Int J Clin Monit Comput 9:95-102, 1992 35. Yafuso M, Arick SA, Hansmann D, et al: Optical pH measurements in blood. Proc SPIE-Int Soc Opt Eng 1067:37-42, 1989 36. Zimmerman JL, Dellinger RP: Initial evaluation of a new intra-arterial blood gas system in humans. Crit Care Med 21:495-500, 1993 Address reprint requests to
Hugh C. Gilbert, MD Division of Anesthesiology Evanston Hospital 2650 Ridge A venue Evanston, IL 60201
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